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DOAJ Open Access 2026
Advances in Stem Cell and Regenerative Medicine for Overcoming Barriers in Tissue Repair and Organ Regeneration

Trivedi Anand, Kumar Gupta Abhishek

This review synthesizes recent advances (2020-2025) in stem cell-based regenerative medicine, focusing on integrating mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and biomaterials to overcome key translational barriers: poor engraftment (<20% in vivo), immunogenicity, and scalability. While Phase II trials demonstrate iPSC-biomaterial constructs achieving 80-90% differentiation efficiency in cartilage and cardiac repair outperforming embryonic stem cells (ESCs) persistent challenges include tumorigenicity, manufacturing variability, and regulatory hurdles. Most importantly, there are contradictions: MSCs are particularly effective in immunomodulation although with mixed results, and 3D bioprinting improves vascularization but falls behind with organoids on clinical scale. Existing gaps in long-term safety data are exemplified, and a model is suggested to enable the prioritisation of selected strategies of autologous iPSC use in terms of ethical limitations, advancing the field past the existing reviews into the realms of the viable application of the strategy to the clinic.

Microbiology, Physiology
DOAJ Open Access 2025
Climate change-induced stress in the honey bee Apis mellifera L.- a genetic review

Soledad Sagastume, Giovanni Cilia, Dora Henriques et al.

Climate change is a powerful driver of stress, as it reinforces hotter and drier environments. For bees, the most concerning aspects of these new environmental conditions are the resistance and resilience of bees to changes in temperature, humidity and ultraviolet radiation, as well as the negative effect on diversity of food resources which can lead in nutritional stress. The climatic vulnerability of various bee species and subspecies varies worldwide, as they experience varying levels of stress and display distinct behaviors, weaknesses, and lifespans. To understand these differences, it is crucial to consider both the genetics and epigenetics of bees, as these factors play a key role in their response, resistance, and adaptation to new stressors. This review provides a guide of genetic and epigenetic markers involved in the cellular response of Apis mellifera to most common stressors derived from climate change. Understanding how the various molecular mechanisms interact to restore homeostasis during the stress response is essential for designing future studies based on molecular markers.

DOAJ Open Access 2025
Effect of Recombinant NGF Encapsulated in Chitosan on Rabbit Sperm Traits and Main Metabolic Pathways

Luigia Bosa, Simona Mattioli, Anna Maria Stabile et al.

The aim of this study was to analyze how recombinant rabbit NGF (Nerve Growth Factor) encapsulated in chitosan (rrβNGFch) affects sperm viability, motility, capacitation, acrosome reaction (AR), kinetic traits, and apoptosis after 30 min and 2 h of storage. Specific intracellular signaling pathways associated with either cell survival, such as protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2), or programmed cell death, such as c-Jun N-terminal kinase (JNK), were also analyzed. The results confirmed the effect of rrβNGFch on capacitation and AR, whereas a longer storage time (2 h) decreased all qualitative sperm traits. AKT and JNK did not show treatment-dependent activation and lacked a correlation with functional traits, as shown by ERK1/2. These findings suggest that rrβNGFch may promote the functional activation of sperm cells, particularly during early incubation. The increase in capacitation and AR was not linked to significant changes in pathways related to cell survival or death, indicating a specific action of the treatment. In contrast, prolonged storage negatively affected all sperm parameters. ERK1/2 activation correlated with capacitation, AR, and apoptosis, supporting its role as an NGF downstream mediator. Further studies should analyze other molecular mechanisms of sperm and the potential applications of NGF in assisted reproduction.

Biology (General)
DOAJ Open Access 2024
Does wet-cupping therapy improve repeated sprint ability, perceived wellness, and rating of perceived exertion in young active males?

Ismail Dergaa, Amine Ghram, Mohamed Romdhani et al.

Wet-cupping therapy (WCT) is one of the oldest known medical techniques, used as a traditional and complementary therapy with a wide application all around the world for general health. Research on the effects of WCT on sports performance are sparse and inconsistent. Thus, we aimed to explore the effects of WCT on repeated sprint ability, wellness, and exertion in young active males. Forty-nine active adult males (age: [28 ​± ​5] years; body height [177 ​± ​8] cm; body mass: [79 ​± ​7] kg; body mass index: [25.4 ​± ​1.8] kg/m2) were selected for the study. The participants performed a running-based sprint test on two separate occasions (Control and Post-WCT). WCT was performed 24 ​h before the testing session. They completed the Hooper questionnaire to assess their well-being (i.e., sleep, stress, fatigue, and soreness) before each session. The rating of perceived exertion (RPE) was collected after each testing session. A higher maximum power (p ​< ​0.05, effect size [ES] ​= ​0.6), mean power (p ​< ​0.01, ES ​= ​0.5) and minimum power (p ​< ​0.01, ES ​= ​0.6) were recorded post-WCT as compared to Control session along with a better perceived sleep (p ​< ​0.01, ES ​= ​0.85). Perceived stress (p ​< ​0.01, ES ​= ​0.6) and RPE (p ​< ​0.001; ES ​= ​1.1) were lower during the post-WCT compared to the Control session. The present findings demonstrated that WCT moderately enhanced repeated sprint ability and had positive effects on perceived sleep, stress, and exertion. WCT may be an effective ergogenic aid to improve repeated sprint ability and general well-being in young adult males. Future large-scale multicentric clinical studies are paramount to confirm the results of our study.

Medicine (General)
DOAJ Open Access 2024
Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood–testis barrier remodeling

Dalia O. Saleh, Sara M. Baraka, Gehad A. Abdel Jaleel et al.

Abstract This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood–testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Medicine, Science
DOAJ Open Access 2023
Microbiome analysis reveals potential for modulation of gut microbiota through polysaccharide-based prebiotic feeding in Oreochromis niloticus (Linnaeus, 1758)

Asit Kumar Bera, Hemanta Chowdhury, Sandeep Ghatak et al.

Characterization and functional profiling of the gut microbiota are essential for guiding nutritional interventions in fish and achieving favorable host-microbe interactions. Thus, we conducted a 30 days study to explore and document the gut microbial community of O. niloticus, as well as to evaluate the effects of a polysaccharide-based prebiotics with 0.5% and 0.75% Aloe vera extract on the gut microbiome through genomic analysis. The V3–V4 region of 16S rRNA was amplified and sequenced using Illumina HiSeq 2500, resulting in 1,000,199 reads for operational taxonomic unit (OTU) identification. Out of 8,894 OTUs, 1,181 were selected for further analysis. Our results revealed that Planctomycetes, Firmicutes, Proteobacteria, Verrucomicrobia, Actinobacteria, and Fusobacteria were the dominant phyla in both control and treatment samples. Higher doses of prebiotics were found to improve Planctomycetes and Firmicutes while decreasing Proteobacteria and Verrucomicrobia. We observed increasing trends in the abundance of Bacilli, Bacillaceae, and Bacillus bacteria at the class, family, and genus levels, respectively, in a dose-dependent manner. These findings were consistent with the conventional colony count data, which showed a higher prevalence of Bacillus in prebiotic-supplemented groups. Moreover, predicted functional analysis using PICRUSt indicated a dose-dependent upregulation in glycolysis V, superpathway of glycol metabolism and degradation, glucose and xylose degradation, glycolysis II, and sulfoglycolysis pathways. Most of the energy, protein, and amino acid synthesis pathways were upregulated only at lower doses of prebiotic treatment. Our findings suggest that the gut microbiome of O. niloticus can be optimized through nutritional interventions with plant-based polysaccharides for improved growth performance in commercial fish.

DOAJ Open Access 2023
Test-re-test reliability and dynamics of the Fukuda–Unterberger stepping test

Simone Hemm, Denise Baumann, Vasco Duarte da Costa et al.

BackgroundThe Fukuda-stepping-test (FST), i.e., repetitive walking on the spot while blindfolded, has been proposed as a means to assess the integrity of the vestibular pathways. While its sensitivity to detect abnormalities in patients is limited, it may be useful in studying the physiology of the subjective-straight-ahead (SSA). Considering reported systematic shifts in SSA in humans, we hypothesize that such asymmetries arise from individual differences in the orientation/configuration of the macular organs and in central processing of vestibular input. We hypothesize that such asymmetries are stable over time in individual subjects. Alternatively, such asymmetries may arise from random noise in the sensory/motor systems involved, demonstrating low reproducibility over time.Materials and methodsTwenty-four subjects walked on the spot over 60 s while blindfolded (n = 6 trials per subject). Using an inertial measurement unit (IMU) placed at the chest, angular deviations were recorded and compared to manually-measured final positions. Both static (direction, magnitude) and dynamic (time-to-onset of deviation, pattern of deviations) parameters were retrieved from the yaw slopes.ResultsSignificant deviations were found in 15/24 participants for the manual measurements (leftwards = 8; rightwards = 7), whereas when using the IMU-sensor 13/24 participants showed significant shifts (leftwards = 9; rightwards = 4). There was a high correlation (0.98) between manually measured rotation angles (average absolute deviations = 58.0 deg ± 48.6 deg; intra-individual variability = 39 deg ± 24 deg) and sensor-based yaw slopes (1.00 deg/s ± 0.88 deg/s; 0.67 deg/s ± 0.41 deg/s). Relevant yaw deviation was detected 22.1 s ± 12.3 s (range = 5.6 s-59.2 s) after the onset of marching (no relevant yaw-deviation in 15/139 measurements), showing a mostly linear behavior over time.ConclusionWe observed significant inter-individual variability in task performance in the FST, reproducing findings from previous studies. With test-re-test reliability being moderate only, but at the same time observing a preference in the side of shifts in most trials and subjects, we conclude that likely both individually varying estimates of straight-ahead and random noise contribute to the pattern of angular deviations observed. Using an IMU-sensory based approach, additional dynamic parameters could be retrieved, emphasizing the value of such a quantitative approach over manual measurements. Such an approach may provide useful additional information to distinguish patients from healthy controls.

Neurology. Diseases of the nervous system
DOAJ Open Access 2022
Acute effects of combined isometric and plyometric conditioning activities on sports performance and tendon stiffness in female volleyball players

Rafał Kalinowski, Anna Pisz, Dominik Kolinger et al.

This study aimed to compare the effects of bilateral and unilateral conditioning activities (CA; combined isometric and plyometric) on countermovement jump performance, modified t-agility test, Achilles tendon stiffness and skin surface temperature. Thirteen female semi-professional volleyball players performed two CAs in random order: 1) bilateral isometric half back squats followed by bilateral drop jumps (BI-CA); and 2) unilateral isometric half back squats followed by unilateral drop jumps (UNI-CA). To assess the effects of CAs, countermovement jump, modified t-agility test, Achilles tendon stiffness and skin surface temperature measurements were performed 5 min before and 6 min after the CA. Both CAs significantly increased thigh skin surface temperature from pre- to post-CA (BI-CA, p &lt; 0.001; effect size [ES] = 1.41 and UNI-CA, p = 0.001; ES = 1.39) but none of them influenced modified t-agility test time (interaction: p = 0.338, main effect of time: p = 0.121 and condition: p = 0.819). The countermovement jump height and modified reactive strength index significantly increased from pre-to post-CA during the BI-CA condition (p = 0.003, ES = 0.45, and p = 0.008, ES = 0.48) but not for UNI-CA (p = 0.061, ES = 0.18 and p = 0.065, ES = 0.26). No significant impact has been found for countermovement depth (interaction: p = 0.054, main effect of time: 0.097, and condition: p = 0.41) as well as for contraction time (interaction: p = 0.536, main effect of time: p = 0.224, and condition: p = 0.807). Moreover, stronger and weaker limb CMJ relative peak force significantly decreased from pre-to post-CA (p = 0.014, ES = −0.31, and p = 0.027, ES = −0.26; respectively) during UNI-CA condition but not for BI-CA (p = 0.096, ES = 0.23, and p = 1.41, ES = 0.18). The stronger and weaker limb Achilles tendon stiffness significantly increased from pre-to post-CA during the UNI-CA condition (p = 0.013, ES = 0.60 and p &lt; 0.001, ES = 0.79; respectively) but not for BI-CA (p = 0.66; ES = 0.15 and p = 0.265; ES = 0.42). Furthermore, the post-CA stronger limb Achilles tendon stiffness during the UNI-CA was significantly higher than that noted during the BI-CA (p = 0.006, ES = 0.7). The present study showed that combined isometric and plyometric bilateral CA effectively improved the countermovement jump but did not enhance the t-agility test performance. These findings indicate that exercise combinations could effectively produce a post-activation performance enhancement effect but should replicate the following explosive task as much as possible.

DOAJ Open Access 2021
Features Of Photosynthesis And Water Regime Of Quercus Pubescens Willd. Under The Conditions Of Autumn Drought Of The Southern Coast Of The Crimea

Ilnitsky O.A., Plugatar Y.V., Pashtetsky A.V. et al.

The objective of the research is to determine the optimal zones and thresholds of soil moisture, temperature, illumination, limiting photosynthesis and transpiration of Quércus pubéscens Willd. and allowing the introduction of the species to other regions. The dependences of the net photosynthesis rate (Pn) and the transpiration rate (E) on stomatal conductivity (gs), leaf temperature (Tl), and soil moisture (Ws) are shown. The ratio of the processes of photosynthesis and respiration, under the influence of soil drought, allowed us to define their optimal values: Ws = 26 – 28%, Pn = 16 –18 μmol/m2c, Rt = 2 – 4 μmol/m2c. The relationship between the net photosynthesis rate, total respiration, and leaf temperature allowed us to determine the temperature maximum of net photosynthesis (the thermal compensation point): Pn = Rt = 2.0 μmol/m2c at Tl = 37ºC. It was found that in the absence of soil drought, the proportion of respiratory costs (Rt/Pg) from true photosynthesis is 20 – 23%, and with soil moisture of 8 – 10% increases to 55 – 58%.

Microbiology, Physiology
DOAJ Open Access 2021
Prognostic nomogram for 30-day mortality of deep vein thrombosis patients in intensive care unit

Runnan Shen, Ming Gao, Yangu Tao et al.

Abstract Background We aimed to use the Medical Information Mart for Intensive Care III database to build a nomogram to identify 30-day mortality risk of deep vein thrombosis (DVT) patients in intensive care unit (ICU). Methods Stepwise logistic regression and logistic regression with least absolute shrinkage and selection operator (LASSO) were used to fit two prediction models. Bootstrap method was used to perform internal validation. Results We obtained baseline data of 535 DVT patients, 91 (17%) of whom died within 30 days. The discriminations of two new models were better than traditional scores. Compared with simplified acute physiology score II (SAPSII), the predictive abilities of two new models were improved (Net reclassification improvement [NRI] > 0; Integrated discrimination improvement [IDI] > 0; P < 0.05). The Brier scores of two new models in training set were 0.091 and 0.108. After internal validation, corrected area under the curves for two models were 0.850 and 0.830, while corrected Brier scores were 0.108 and 0.114. The more concise model was chosen to make the nomogram. Conclusions The nomogram developed by logistic regression with LASSO model can provide an accurate prognosis for DVT patients in ICU.

Diseases of the circulatory (Cardiovascular) system
DOAJ Open Access 2021
Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair

Shintaro Ide, Yoshihiko Kobayashi, Kana Ide et al.

Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, we show that proximal tubular (PT) cells develop a molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT cells transiently appear after mild injury and return to their original state without inducing fibrosis, after severe injury they accumulate and contribute to persistent inflammation. This transient inflammatory PT state significantly downregulates glutathione metabolism genes, making the cells vulnerable to ferroptotic stress. Genetic induction of high ferroptotic stress in these cells after mild injury leads to the accumulation of the inflammatory PT cells, enhancing inflammation and fibrosis. Our study broadens the roles of ferroptotic stress from being a trigger of regulated cell death to include the promotion and accumulation of proinflammatory cells that underlie maladaptive repair.

Medicine, Science
DOAJ Open Access 2021
The Differentiation in Image Post-processing and 3D Reconstruction During Evaluation of Carotid Plaques From MR and CT Data Sources

Fengbin Deng, Changping Mu, Ling Yang et al.

Background: Carotid plaque morphology and tissue composition help assess risk stratification of stroke events. Many post-processing image techniques based on CT and MR images have been widely used in related research, such as image segmentation, 3D reconstruction, and computer fluid dynamics. However, the criteria for the 3D numerical model of carotid plaque established by CT and MR angiographic image data remain open to questioning.Method: We accurately duplicated the geometry and simulated it using computer software to make a 3D numerical model. The initial images were obtained by CTA and TOF-MRA. MIMICS (Materialize’s interactive medical image control system) software was used to process the images to generate three-dimensional solid models of blood vessels and plaques. The subsequent output was exported to the ANSYS software to generate finite element simulation results for the further hemodynamic study.Results: The 3D models of carotid plaque of TOF-MRA and CTA were simulated by using computer software. CTA has a high-density resolution for carotid plaque, the boundary of the CTA image is obvious, and the main component of which is a calcified tissue. However, the density resolution of TOF-MRA for the carotid plaque and carotid artery was not as good as that of CTA. The results show that there is a large deviation between the TOF-MRA and CTA 3D model of plaque in the carotid artery due to the unclear recognition of plaque boundary during 3D reconstruction, and this can further affect the simulation results of hemodynamics.Conclusion: In this study, two-dimensional images and three-dimensional models of carotid plaques obtained by two angiographic techniques were compared. The potential of these two imaging methods in clinical diagnosis and fluid dynamics of carotid plaque was evaluated, and the selectivity of image post-processing analysis to original medical image acquisition was revealed.

DOAJ Open Access 2020
Effects of High-Intensity Resistance Training and Aerobic Exercise on Expression of ABCG4, ABCG5 and ABCG8 Genes in Female Athletes

Reza Bagheri, Samane Darroudi, S Mojtaba Hosseini et al.

Background and objectives: Atherosclerotic cardiovascular disease is the leading cause of death in industrialized countries. High level of plasma lipids including cholesterol and triglycerides is one of the most important risk factors of atherosclerosis. Previous studies have shown that three members of the ATP-binding cassette, subfamily G (ABCG4, ABCG5 and ABCG8) are involved in transporting sterols across membranes. The purpose of this study was to assess the effect of high-intensity resistance training (HIRT) and aerobic exercise (AE) on expression of the ABCG4, ABCG5 and ABCG8 genes in female athletes. Methods: Twenty-four female athletes from the Khorasan Province (Iran) were randomly selected and assigned into three groups: control (N=8), AE (N=8) and HIRT (N=8). The subjects in the HIRT group and the AE group performed exercise at intensity of 75-80% of 1-repetion maximum and 75-80% of maximum heart rate, respectively. Blood samples were collected at baseline and immediately after the exercise session. After isolation of lymphocytes by centrifugation and purification of mRNA, gene expression changes were investigated by Real-Time-PCR. Data were analyzed using one-way ANOVA and the Tukeychr('39')s test. Results: Both training protocols significantly increased the expression of ABCG4, ABCG5 and ABCG8 in the subjects (P<0.05), and there was no significant difference in the expression of these genes between the experimental groups (P>0.05). Conclusion: A single session of HIRT and AE may have beneficial effects on prevention of atherosclerosis.

DOAJ Open Access 2019
Colonización de sustratos artificiales y naturales por hongos acuáticos zoospóricos

Agostina Virginia Marano, Mónica Mirta Steciow

We study the in situ colonization of different kinds of substrata by zoosporic fungi (S.D Mastigomycotina), making weekly samplings during a month in the streams «El Zanjón» and «Las Cañas» (Ensenada, Bs. As., Argentina). In those sites we put twelve different substrata, both naturals (monocotyledon leaves, crustacean shells, Rosa sp. fruits, snake sheds and little fishes) and artificial ones (cellophane fragments, polypropylene bags, slides, and two kinds of different plastic materials). The substrata were put separately in drilled plastic bags, and left for a week to allow colonization. In both sites, we observed that Saprolegnia colonized every kind of substratum (both natural and artificial ones), while Achlya was encountered in the majority of them (little fishes, slides, cellophane fragments, pieces of X-rays, Rosa sp. fruits, and monocotyledon leaves), Dichtyuchus was observed in fishes and Rosa sp. fruits, Brevilegnia and Pythium in pieces of X-rays plate and Aphanomyces only in plastic materials. Based on these preliminary results, we can infer that there is an apparent selection of some genera for particular substrata. It’s interesting to emphasize that colonization of artificial substrata by Saprolegnia, Achlya, Brevilegnia, Pythium and Aphanomyces, might suggest the possibility of using these genera in superficial biodegradation of plastic materials.

Aquaculture. Fisheries. Angling, Biology (General)
DOAJ Open Access 2019
Relevamiento sociodemográfico del aprovechamiento de la fauna íctica en la cuenca inferior del río Luján

Paula Courtalón, Gabriela Gerardo, Liliana Ciotek

El objetivo general del presente trabajo fue identificar las especies de peces que capturan los pescadores y el uso que le dan a las mismas en la cuenca inferior del río Luján. Para tal fin, se realizaron entrevistas semiestructuradas durante la primavera de 2015, el verano y el otoño 2016, las cuales permitieron obtener información sobre el uso que les dan los pescadores a los peces capturados. Se analizaron a lo largo de este período dos escenarios: los días de semana y los fines de semana. En la cuenca inferior del río Luján coexiste una diversidad de contextos sociales manifestados a través de sus actores: los pobladores locales y los pobladores de partidos vecinos que visitan el área. Las especies más mencionadas a lo largo de todo el estudio fueron: Pimelodus maculatus, Pimelodus albicans, Astyanax sp., Megaleporinus obtusidens y Rhamdia quelen. Los resultados obtenidos permiten plantear la importancia que tiene este territorio en la ribera del río Luján para los pobladores de la zona y de las regiones cercanas dado que los días de semana es un sitio que ofrece un espacio para realizar pesca de subsistencia mientras que los fines de semana constituye un espacio para el esparcimiento familiar.

Aquaculture. Fisheries. Angling, Biology (General)
DOAJ Open Access 2019
NFAT5 and HIF-1α Coordinate to Regulate NKCC1 Expression in Hippocampal Neurons After Hypoxia-Ischemia

Xing-Liang Yang, Meng-Liu Zeng, Lin Shao et al.

Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with severe long-term sequelae such as cerebral palsy, epilepsy and cognitive disabilities. Na+-K+-2Cl– cotransporters 1 (NKCC1) is dramatically upregulated after hypoxia-ischemia (HI), which aggravates brain edema and brain damage. Clinically, an NKCC1-specific inhibitor, bumetanide, is used to treat diseases related to aberrant NKCC1 expression, but the underlying mechanism of aberrant NKCC1 expression has rarely been studied in HIE. In this study, the cooperative effect of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor of activated T cells 5 (NFAT5) on NKCC1 expression was explored in hippocampal neurons under hypoxic conditions. HI increased HIF-1α nuclear localization and transcriptional activity, and pharmacological inhibition of the HIF-1α transcription activity or mutation of hypoxia responsive element (HRE) motifs recovered the hypoxia-induced aberrant expression and promoter activity of NKCC1. In contrast, oxygen–glucose deprivation (OGD)-induced downregulation of NFAT5 expression was reversed by treating with hypertonic saline, which ameliorated aberrant NKCC1 expression. More importantly, knocking down NFAT5 or mutation of the tonicity enhancer element (TonE) stimulated NKCC1 expression and promoter activity under normal physiological conditions. The positive regulation of NKCC1 by HIF-1α and the negative regulation of NKCC1 by NFAT5 may serve to maintain NKCC1 expression levels, which may shed light on the transcription regulation of NKCC1 in hippocampal neurons after hypoxia.

Biology (General)
DOAJ Open Access 2019
Modular organization of cerebellar climbing fiber inputs during goal-directed behavior

Shinichiro Tsutsumi, Naoki Hidaka, Yoshikazu Isomura et al.

The cerebellum has a parasagittal modular architecture characterized by precisely organized climbing fiber (CF) projections that are congruent with alternating aldolase C/zebrin II expression. However, the behavioral relevance of CF inputs into individual modules remains poorly understood. Here, we used two-photon calcium imaging in the cerebellar hemisphere Crus II in mice performing an auditory go/no-go task to investigate the functional differences in CF inputs to modules. CF signals in medial modules show anticipatory decreases, early increases, secondary increases, and reward-related increases or decreases, which represent quick motor initiation, go cues, fast motor behavior, and positive reward outcomes. CF signals in lateral modules show early increases and reward-related decreases, which represent no-go and/or go cues and positive reward outcomes. The boundaries of CF functions broadly correspond to those of aldolase C patterning. These results indicate that spatially segregated CF inputs in different modules play distinct roles in the execution of goal-directed behavior.

Medicine, Science

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